Emphysema appears to result from pathologic elastin degradation. Elastin can be degraded when lung phagocytes release more enzymes than can be inhibited by local antiproteases. Since lung elastin fibers are located in the interstitial space, specific knowledge of the interstitial antiproteases is crucial to understanding the antielastolytic mechanisms of the lung. My preliminary data indicates that the interstitium has a higher antiprotease activity (trypsin inhibitory capacity) than does plasma. That data additionally indicates that biochemically similar antiproteases are in both pools. The current study addresses the hypothesis that antiproteases, or antiprotease activators, produced in the lung help protect the lung from elastolytic degradation. I will use the "essentially pure" lung lymph from the sheep lung lymph fistula preparation to quantitate the interstitial alpha-1-antitrypsin and alpha-2-macroglobulin levels and thus permit comparison of the plasma and interstitial antiproteases. In order to define plasma antiprotease filtration into the interstitium I will compare the steady-state lymph-to-plasma ratios of intravenously infused radio-labelled antiproteases and total interstitial antiproteases. The size and direction of the concentration gradient between plasma and the interstitium will determine the filtration between the two pools. I will change the systemic antiprotease levels, define the effect of those changes on the interstitial antiprotease concentrations and then instill elastase intratracheally to define the importance of interstitial alpha-1-antitrypsin and alpha-2-macroglobulin in preventing lesion development. Defining the pulmonary anti-elastolytic mechanisms will help in designing prophylactic treatments for high risk populations.